Gene expression evidence for remodeling
of lateral hypothalamic circuitry in cocaine addiction
by
Ahmed SH, Lutjens R, van der Stap LD, Lekic D, Romano-Spica V,
Morales M, Koob GF, Repunte-Canonigo V, Sanna PP.
Department of Neuropharmacology, M
The Scripps Research Institute, La Jolla, CA 92103.
Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11533-8

ABSTRACT

By using high-density oligonucleotide arrays, we profiled gene expression in reward-related brain regions of rats that developed escalated cocaine intake after extended access to cocaine (6 h per day). Rats allowed restricted daily access to cocaine (only 1 h) that displayed a stable level of cocaine intake and cocaine naive rats were used for controls. Four analysis methods were compared: Affymetrix microarray suite 4 and microarray suite 5, which use perfect-match-minus-mismatch models, and dchip and rma, which use perfect-match-only models to generate expression values. Results were validated by RT-PCR in individual animals from an independent replication of the experiment. A small number of genes was associated with escalated cocaine intake (ESC genes). Unexpectedly, of the brain regions examined [prefrontal cortex, nucleus accumbens, septum, lateral hypothalamus (LH), amygdala, and ventral tegmental area], the LH was the most transcriptionally responsive in escalation of cocaine intake. Most of the ESC genes identified are also expressed during synaptogenesis and synaptic plasticity and include genes that code for several presynaptic and postsynaptic proteins involved in neurotransmission. These results suggest that LH intrinsic circuitry undergoes a structural reorganization during escalation of cocaine use. This remodeling of LH circuitry could contribute to the chronic deficit in reward function that has been hypothesized to drive the transition to drug addiction. Results also support the value of using multiple analysis strategies to identify the most robust changes in gene expression and to compensate for the biases that affect each strategy.

History
Inca tea
Oral cocaine
The coke-craving brain
Cocaine and depression
Cocaine and the lonely rat
Gene expression profiles: heroin v cocaine

01 02 03 04 05 06 07 08 09 10 11 12
13 14 15 16 17 18 19 20 21 22 23 24

Refs
HOME
HedWeb
Future Opioids
BLTC Research
Utopian Surgery?
The Hedonistic Imperative
MDMA: Utopian Pharmacology
When Is It Best to Take Crack Cocaine?

The Good Drug Guide
The Responsible Parent's Guide To
Healthy Mood Boosters For All The Family